The main objective of this study is to use the quantitated measurement of thyroglobin in unextracted serum (HTg)as a sensitive indicator of the presence of a thyroid malignancy or metastases thereof. Therefore we propose to study the release of HTg in the circulation of subjects with thyroid tumors. Serum levels in patients with benign and malignant neoplasms of the thyroid will be investigated. Sera from patients with a thyroid neoplasm will be assayed for thyroglobulin (HTg) using a specific radioimmunoassay for this protein. This technique has recently been developed in our laboratories and levels in normal individuals have been firmly established. In patients in which a malignant thyroid tumor was removed previously, HTg levels will be determined and compared with conventional radioisotope scanning techniques. In addition to the effect of conventional therapy (131 1 and surgery) the effect of chemotherapy (Adriamycin) on levels will be studied. In order to rule out other causes of elevated HTg levels such as hyperthyroidism, the functional status of the thyroid will be firmly established and T4 and T3 measurements will be carried out in each case under investigation. From these studies it is hoped to use the information provided by the secreted marker substance (HTg) a) to detect the presence of microfoci of tumor, b) to quantitate the total amount of tumor in the body, c) to demonstrate recurrences after treatment, d) to gauge the effects of treatment, e) to assess the mechanisms by which the marker is released by the tumor.